On November 28, 2022, Hangzhou Polymed Biopharmaceuticals Co., Ltd. (Hangzhou Polymed Biopharmaceuticals, hereinafter referred to as "Polymed") reported the commencement of the Pre-A+ round of financing jointly invested by Cybernaut Investment and ZJKF Capital Management Co. , Ltd (ZJKF Capital) (Press release, Polymed Biopharmaceuticals, NOV 28, 2022, View Source [SID1234630625]). The funds obtained from this round of financing will be used to support the IND submission and clinical trial planning of the company’s two preclinical candidate compounds (PCCs).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Based in Hangzhou with offices in Shanghai and Boston, Polymed is focused on discovery and development of novel drugs for high unmet medical need in cancer and autoimmune disease. Polymed’s differentiated discovery platform is designed to tackle "undruggable" drug targets using bifunctional molecules especially PRTOACs. The core leadership team of Polymed consists of three experts with more than 20 years of experience working in top international pharmaceutical companies such as Novartis and Pfizer for new drug research and development. Polymed has established a rich product pipeline on PROTAC and small molecule inhibitors.

Unlike conventional small molecule inhibitors, PROTACs are bifunctional molecules that remove disease causing abnormal proteins through the proteasomal degradation pathway. PROTACS can be applied to a wide range of targets including those that are intractable by conventional small molecules. Polymed’s PROTAC platform is built upon a unique and proprietary linker library that can be used for rapid optimization of PROTACs. Polymed has further combined the PROTAC approach with state of the art technologies such as artificial intelligence, structure biology and proteomics. This platform has been validated for multiple targets, including a preclinical candidate with proof of concept efficacy and safety data in animal models.

The company has also made a major breakthrough of bifunctional small molecule inhibitors. At present, a candidate compound with unique inhibition profile and excellent pharmaceutical properties has been established, and CMC work has been initiated. The new round of funding will enable the advancement of the preclinical program to the clinic, aiming at advancement of the lead programs to preclinical proof of concept and further development of the platform.

Dr. Jason Shaoyun Xiang, founder and CEO of Polymed, believes that the development of new PROTAC drugs is a disruptive technological innovation, and its potential impact may be comparable to that of therapeutic antibodies two decades ago and mRNA vaccines today, bringing about a wave of novel therapeutics. This disruptive technological breakthrough will undoubtedly bring great benefits to patients, and reward those visionary supporters. Dr. Xiang sincerely thanks the team of Cybernaut, Kefa and Matrix Partners for their firm trust in and support to Polymed. Polymed will make full use of its team experience and international advantages to rapidly advance the research and development progress of various projects, and strive to develop more efficacious therapeutics for patients as soon as possible.

Kaixuan Liu, vice president of Cybernaut Investment, said that the evolution of new small molecule drug discovery has continued from the previous wave of kinase inhibitors to the current wave of protein degradation agents. We are very optimistic about the revolutionary breakthrough that PROTAC technology will bring to the pharmaceutical industry. The Polymed team led by Dr. Xiang has world-class cutting-edge research and practical experiences in medicinal chemistry and the biology of innate immune pathway targets, which will enable the fruitful R & D efforts for company’s PROTAC pipelines.

Gao Chen, vice president of ZJKF Capital, said that PROTAC technology breaks through the drug design concept of inhibition, addresses the traditional "undruggable" target problems and endows small molecule drugs with a new mode of action. It is considered as a Revolutionary technology in the field of biomedicine. The Polymed’s founding team has accumulated many years of experiences in the field of PROTAC, developed multiple technical platforms for PROTAC drug design, and screened out a number of highly competitive candidate compounds. We are very please to work with Polymed, and believe that Polymed is destined to become an innovative biomedical technology company with global influence, bringing breakthrough therapeutics to patients in the field of tumor and autoimmunity.

Dr. Zhiyun Yu, a partner of Matrix Partners, said that Polymed not only has a rich small molecule new drug pipeline but also has corresponding PROTAC technology: its small molecule new drug has the potential of being first in class or best in class in China, and we are optimistic about its potential in the upcoming clinical development. PROTAC technology is one of the key areas of focus for Matrix. It has been initially validated internationally but is still in the early stage of rapid development in China. It has broad application prospects in difficult-to-drug targets.

On November 28, 2022 Replay, a genome writing company reprogramming biology by writing and delivering big DNA, reported that it has received a $1.56 million grant from the Bill & Melinda Gates Foundation to accelerate the development of uCell, a proprietary hypoimmunogenic technology platform (Press release, Replay, NOV 28, 2022, View Source [SID1234627367]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Replay’s uCell platform is an off-the-shelf, genomically rewritten, hypoimmunogenic technology that allows allogeneic donor-derived primary cells and iPSCs (Induced Pluripotent Stem Cells) to be made immune silent. The technology is expected to substantially decrease the cost-of-goods of cell therapies, improve product volume and consistency, enable extensive genome engineering, and in the case of cancer cell therapy, enable deeper clinical responses and reduced relapse rates. uCell is anticipated to form the basis of several off-the-shelf iPSC-derived immune cell therapies applicable to a multiple therapeutic areas, including cancer and infectious diseases. The technology is relevant to both the developed and developing worlds, with the anticipated reduced cost-of-goods improving equity of access.

Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay, commented: "Hypoimmunogenic technology is the ‘holy grail’ of cell therapy and the non-dilutive funding received from the Bill & Melinda Gates Foundation will help accelerate the development of our uCell technology. It is expected to address many of the key challenges of cell therapy, including scalability, the ability to introduce extensive genomic modifications, and need to reduce cost-of-goods. We are immensely grateful to the foundation and our investors for supporting Replay’s vision for the future of genomic medicine, which includes a focus on the development of high-impact and affordable cell therapies that are accessible to both industrialized and rural communities."

Lachlan MacKinnon, Chief Executive Officer, and Co-Founder of Replay, added: "Replay’s hypoimmunogenic technology is the result of a convergence of synthetic biology, computational design, and protein engineering with iPS cell technology. It will enable the Company to develop a universal off-the-shelf platform in a reliable, scalable, and cost-effective manner, and broaden the utility and accessibility of cell therapy, including regenerative medicine applications. The ability to reprogram hypoimmunogenic iPSCs with our high payload synHSV platform will unlock a differentiated set of opportunities. As is the case with synHSV, and given the substantive opportunity in the space, we plan to progress our uCell technology through distinct therapeutic area-focused product companies."

Professor Herman Waldmann, Co-inventor of uCELL and Emeritus Professor of Pathology at the Sir William Dunn School of Pathology at the University of Oxford, said: "As a physician scientist, it is encouraging to see Replay advance the uCell platform, which has the potential to overcome many of the current limitations of cell therapies. By making iPSCs immune silent to generate a universal cell with utility as a renewable source for cell therapies, uCell has the potential to bring the benefits of this important therapeutic modality to patients across the world."

On November 28, 2022 Exscientia plc (Nasdaq: EXAI) reported clinical trial application (CTA) approval of IGNITE-AI, enabling site activation in its first European country. IGNITE-AI is a Phase 1/2 trial studying EXS-21546 (‘546), Exscientia’s A2A receptor antagonist in combination with anti-PD-1 therapy in patients with immunotherapy relapsed or refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) (Press release, Exscientia, NOV 28, 2022, View Source [SID1234624876]). The study will evaluate safety, efficacy, pharmacokinetics and pharmacodynamics in up to 110 patients. Exscientia intends to expand to additional tumour types, including breast cancer, in future trials after assessment of ‘546 activity and validation of its selection biomarkers.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"High adenosine levels in the tumour microenvironment have the potential to suppress immune function, which can inhibit the efficacy of checkpoint inhibitors," said Dr. Michael Krams, Chief Quantitative Medicine Officer of Exscientia. "We have designed this trial not only to learn about ‘546, but also to enhance our confidence in our patient enrichment strategy. We place a strong emphasis on biomarker qualification, because our goal is to identify the right patients for the right treatment."

Exscientia used simulation guided clinical trial design to determine the operating characteristics of the two stages of the trial. The first stage will apply a continuous reassessment model to use accruing data from the dose escalation phase to establish the maximum tolerated dose (MTD) of Exscientia’s A2A receptor antagonist. Once the MTD is identified with sufficient confidence, the study will advance to the second stage, where the MTD is applied to an expansion cohort. The goal of the expansion phase is to create evidence of efficacy of ‘546 in combination with a PD-1 inhibitor as well as further enhance confidence in Exscientia’s biomarker signature.

At a medical meeting in December, Exscientia will present data on its novel multi-gene signature for identifying high adenosine patient populations, referred to as the adenosine burden score (ABS). IGNITE-AI is designed to prospectively evaluate the ABS in comparison to patient responses in order to validate its use in patient selection. Once statistical confidence in the ABS has been reached, the Company plans to apply the biomarker signature to directly enrich the patient population in clinical development.

"We are proud to move forward with this industry-leading trial and the first patient study for Exscientia. Exscientia is a precision medicine company, and this trial exemplifies how we are extending our AI-driven, adaptive learning approach that we use in discovery now into development," said Professor Andrew Hopkins, D.Phil., founder and Chief Executive Officer of Exscientia. "We believe that our precision medicine platform can help us select the right patients, which could allow us to translate the scientific potential for A2A receptor antagonists into clinical results."

About the Phase 1/2 IGNITE-AI trial

The IGNITE-AI Phase 1/2 trial is a multicentre, open-label, two-stage clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of EXS-21546 in combination with PD-1 inhibition. The Company intends to enrol patients with relapsed or refractory RCC or NSCLC who previously received treatment with an immune checkpoint inhibitor. By evaluating patients that have progressed after checkpoint inhibition therapy, the trial is designed to test whether A2A receptor antagonism will restore the ability of the immune system to respond to checkpoint inhibitors.

The dose escalation portion of the trial will enrol a maximum of 30 patients across up to seven dose levels, depending on how many dose levels are needed to define the maximum tolerated dose (MTD). The dose expansion phase of the trial will commence upon identification of the MTD and will enrol up to 80 patients. The primary efficacy endpoint of the expansion phase is objective response rate (ORR).

EXS-21546 is a highly selective A2A receptor antagonist ​​co-invented and developed through a collaboration between Exscientia and Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; Nasdaq: EVO). The molecule was identified in 9 months after testing 163 compounds and is one of the first AI designed drugs in the industry to enter the clinic. In June 2022, Exscientia reported topline data from a healthy volunteer study which confirmed Exscientia’s target product profile design, including potency, high receptor selectivity and expected low brain exposure with no CNS adverse events reported.

On November 28, 2022 Ikena Oncology, Inc. (Nasdaq: IKNA, "Ikena"), a targeted oncology company forging new territory in patient-directed cancer treatment, reported that a next-generation mitogen-activated protein kinase (MEK)-RAF complex inhibitor, IK-595, has been nominated as the company’s first development candidate in the RAS pathway (Press release, Ikena Oncology, NOV 28, 2022, View Source [SID1234624641]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The RAS pathway is implicated in at least half a million new cancer diagnosis each year in the United States alone. Ikena aims to target the pathway on multiple levels, including preventing known resistance mechanisms to achieve deep and sustained responses. Ikena’s new development candidate, IK-595, traps MEK and RAF in an inactive complex, more completely inhibiting RAS signals than existing inhibitors. IK-595’s ability to complex CRAF, in particular, prevents a well-recognized signaling bypass mechanism that cancer cells employ to drive therapeutic resistance to other drugs in this class. In addition, trapping CRAF in an inactive complex prevents the kinase independent anti-apoptotic function in RAS and RAF mutant cancers, a mechanism that cannot be addressed with first generation MEK inhibitors or pan-RAF inhibitors. IK-595 is being developed as an oral therapy, with a half-life enabling a pharmacokinetic profile potentially superior to other drugs, with the goal of developing an optimal therapeutic window for patients. The company plans to submit an investigational new drug application (IND) for IK-595 to the US Food & Drug Administration (FDA) in the second half of 2023.

"I am thrilled to announce this addition to our pipeline, one that adds to our holistic approach to the Hippo & RAS oncosignaling network. IK-595 inhibits multiple nodes of MEK-RAF signaling, including avoiding known mechanisms of resistance," said Mark Manfredi, PhD, Ikena’s Chief Executive Officer. "The industry’s excitement about MEK inhibition stems from its great potential as a target, but the challenges of CRAF bypass and achieving optimal target inhibition have kept first generation treatments from meeting the full potential of the target. We are hopeful that our MEK-RAF trapping approach with an optimized therapeutic window can make IK-595 a game-changing candidate for multiple indications in the RAS space."

Development Highlights, Corporate Updates, and Upcoming Milestones

Advancing new development candidate, IK-595, through IND-enabling studies, targeting MEK-RAF through novel mechanisms aiming to address existing gaps in the MEK inhibitor space
Preclinical differentiation data planned for presentation in the first half of 2023
IND targeted in the second half of 2023
Progressing novel, paralog-selective transcriptional enhanced associate domain (TEAD) inhibitor, IK-930, in the clinic and further defining differentiation profile from panTEAD inhibition
Monotherapy program progressing as planned, advanced through multiple dose escalation cohorts
Preclinical data on differentiation and advantages of paralog selectivity planned for presentation in first half of 2023
Initiation of osimertinib combination cohort clinical program expected in first half of 2023
Initial clinical data from IK-930 monotherapy program expected in second half of 2023
Following a portfolio review, discontinuing the internal clinical development of the EP4 antagonist IK-007 and exploring strategic alternatives for this program
Clinical data from IK-007 in microsatellite stable colorectal cancer (MSS-CRC) will be presented in a poster at 2022 European Society for Medical Oncology Immuno-Oncology Congress
Portfolio reprioritization and streamlining of discovery and clinical activities contribute to extension of cash runway into 2025
Runway does not include any potential licensing revenue from the aryl hydrocarbon receptor (AHR) antagonist IK-175 program, currently in development in collaboration with Bristol Myers Squibb and eligible for opt-in through early 2024
"Ikena has a strong track record of internal drug discovery and development that has built our robust clinical and early-stage pipeline," said Jotin Marango, MD, PhD, Chief Financial Officer and Head of Corporate Development of Ikena. "Our goal is to continue our leadership in targeted oncology by discovering and advancing best-in-class candidates like IK-930 and IK-595, therapies designed to address the needs of specific patient populations while at the same time building value for our shareholders."

On November 28, 2022 Alaunos Therapeutics, Inc. ("Alaunos" or the "Company") (Nasdaq: TCRT), a clinical-stage oncology-focused cell therapy company, reported that it has commenced an underwritten public offering of its common stock (Press release, Alaunos Therapeutics, NOV 28, 2022, View Source [SID1234624621]). In addition, Alaunos expects to grant to the underwriter a 30-day option to purchase up to an additional 15% of shares of the common stock sold in the public offering. All of the securities in the offering are to be sold by Alaunos. The offering is subject to market and other customary closing conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Alaunos intends to use the net proceeds from the proposed offering to fund the continued development of the product candidates in its pipeline, and for working capital, capital expenditures and general corporate purposes.

Cantor Fitzgerald & Co. is acting as the sole book-running manager for the offering.

A registration statement on Form S-3 (No. 333-266841) relating to these securities has been filed with the U.S. Securities and Exchange Commission (the "SEC") and was declared effective on September 7, 2022. The offering will be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement related to the offering has been filed with the SEC and is available free of charge by visiting EDGAR on the SEC’s website at www.sec.gov.

Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering may be obtained free of charge from Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Ave., 4th Floor, New York, New York 10022, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Any offers, solicitations or offers to buy, or any sales of securities will be made in accordance with the registration requirements of the Securities Act of 1933, as amended.